The incidence and mortality of melanoma has been increasing more rapidly than any other malignancy except lung cancer in women. Although many cases can be classified reliably with current pathological criteria, there is a significant subset of cases in which no consensus can be reached even among expert pathologists. The effect of the ambiguity on standard clinical practice is illustrated in a study from The Netherlands. An expert panel reviewed 1069 consecutive melanocytic lesions that had been submitted for review by clinical pathologists in order to identify the most common diagnostic problems. In 14% (22/158) of the cases that had been initially classified as invasive melanoma the panel considered the lesions as benign, and in 16.6% (85/513) the panel considered malignant what had been diagnosed as benign (Veenhuizen et al., J Pathol. 182:266-72. 1997).
Diagnostic ambiguity has significant adverse consequences for patients. Misclassifying a melanoma as benign may be fatal, and diagnosing a benign lesion as malignant may result in significant morbidity. Current medical practice with equivocal cases usually is to consider them as malignant. However, the morbidity of the therapeutic options—wide re-excision, sentinel lymph node biopsy, and adjuvant alpha-interferon—coupled with the diagnostic uncertainty frequently leads to pursuing a less aggressive treatment regimen. Typically this includes a limited re-excision and close clinical follow-up. Thus patients with benign lesions suffer the side effects of a still significant surgery and the emotional strain of the diagnosis, while those patients that in fact have a melanoma may not receive the optimal treatment. Currently there is no method to definitively resolve these ambiguities. A diagnostic test that could reduce these uncertainties would have a significant positive clinical impact.
Previous studies have shown that melanomas differ from nevi by the presence of frequent gains or losses of particular chromosomal regions. Comparative genomic hybridization (CGH) of primary melanomas has identified losses at 6q, 8p, 9p, and 10q and gains at 1q, 6p, chromosome 7, 8q, 17q, and 20q to be the most common DNA copy number changes in melanoma (Bastian et al, Am J Pathol. 163:1765-70, 2003). However, there is a need for further refinement of diagnostic techniques that evaluate chromosome copy number changes so that a melanoma can be more accurately characterized. This invention addresses that need.